No further evidence of an increased risk of infant neural tube defects related to the use of dolutegravir or other integrase inhibitors in early pregnancy has emerged in safety reviews conducted over the past few months, researchers reported at the International Congress on Drug Therapy in HIV Infection (HIV Glasgow) on Monday.
The potential risk of a harmful effect of the integrase inhibitor dolutegravir on foetal neurological development was flagged up after an increased incidence of neural tube defects was observed in the infants of mothers who had been taking dolutegravir at the time of conception in Botswana. The World Health Organization subsequently issued guidance to national treatment programmes which suggested that dolutegravir-based regimens should be avoided by women of childbearing potential unless they had adequate contraception in place.
Investigators have stressed that what was observed was a safety signal that needs to be investigated, and that more evidence is needed before investigators can say for certain that dolutegravir increases the risk of neural tube defects if taken at the time of conception or in the first trimester (first three months) of pregnancy. Further follow-up from the prospective Botswana study will be reported in March 2019.
The safety signal also raised questions about the safety of other integrase inhibitors. Raltegravir (Isentress) has been used widely in the United States and Europe since 2008 but there is no evidence that its use is associated with an increased risk of neural tube defects.
Neural tube defects occur when the development of the spinal cord, the brain and the skull is impaired during the early weeks of pregnancy. The most frequent cause of these defects is a deficiency in folate, so pregnant women are advised to take a folic acid supplement. Exposure to some drugs around the time of conception and during the early weeks of pregnancy may cause neural tube defects.